Su Chih-Chia, Bolla Jani Reddy, Kumar Nitin, Radhakrishnan Abhijith, Long Feng, Delmar Jared A, Chou Tsung-Han, Rajashankar Kanagalaghatta R, Shafer William M, Yu Edward W
Department of Physics and Astronomy, Iowa State University, Ames, IA 50011, USA.
Department of Chemistry, Iowa State University, Ames, IA 50011, USA.
Cell Rep. 2015 Apr 7;11(1):61-70. doi: 10.1016/j.celrep.2015.03.003. Epub 2015 Mar 26.
Neisseria gonorrhoeae is an obligate human pathogen and the causative agent of the sexually transmitted disease gonorrhea. The control of this disease has been compromised by the increasing proportion of infections due to antibiotic-resistant strains, which are growing at an alarming rate. N. gonorrhoeae MtrF is an integral membrane protein that belongs to the AbgT family of transporters for which no structural information is available. Here, we describe the crystal structure of MtrF, revealing a dimeric molecule with architecture distinct from all other families of transporters. MtrF is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins, posing a plausible pathway for substrate transport. A combination of the crystal structure and biochemical functional assays suggests that MtrF is an antibiotic efflux pump mediating bacterial resistance to sulfonamide antimetabolite drugs.
淋病奈瑟菌是一种专性人类病原体，也是性传播疾病淋病的病原体。由于抗生素耐药菌株导致的感染比例不断增加，且其增长速度惊人，这使得该疾病的控制受到了影响。淋病奈瑟菌MtrF是一种整合膜蛋白，属于AbgT转运蛋白家族，目前尚无该家族的结构信息。在此，我们描述了MtrF的晶体结构，揭示了一种二聚体分子，其结构与所有其他转运蛋白家族不同。MtrF是一个碗状二聚体，有一个从细胞质延伸到膜双层一半位置的充满溶剂的盆状结构。该转运蛋白的每个亚基包含九个跨膜螺旋和两个发夹结构，为底物运输提供了一条合理的途径。晶体结构和生化功能分析表明，MtrF是一种抗生素外排泵，介导细菌对磺胺类抗代谢药物的耐药性。
